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Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells
The MOG35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice is a useful animal model to explore therapeutic approaches to T cell-mediated autoimmune diseases because the dominant T-cell epitope(s) have been defined. It is rational that antigen-specific immunosu...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471819/ https://www.ncbi.nlm.nih.gov/pubmed/23077616 http://dx.doi.org/10.1371/journal.pone.0047435 |
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author | Gong, Yeli Wang, Zhigang Liang, Zhihui Duan, Hongxia Ouyang, Lichen Yu, Qian Xu, Zhe Shen, Guanxin Weng, Xiufang Wu, Xiongwen |
author_facet | Gong, Yeli Wang, Zhigang Liang, Zhihui Duan, Hongxia Ouyang, Lichen Yu, Qian Xu, Zhe Shen, Guanxin Weng, Xiufang Wu, Xiongwen |
author_sort | Gong, Yeli |
collection | PubMed |
description | The MOG35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice is a useful animal model to explore therapeutic approaches to T cell-mediated autoimmune diseases because the dominant T-cell epitope(s) have been defined. It is rational that antigen-specific immunosuppression can be induced by using MHC-peptide complexes as specific TCR ligand(s) that interact with autoreactive T cells in the absence of co-stimulation. In this study, a soluble divalent MOG35-55/I-A(b) fusion protein (MOG35-55/I-A(b) dimer) was constructed to specifically target the autoreactive CD4(+) T cells in the EAE mouse. Intraperitoneal administration of the MOG35-55/I-A(b) dimer significantly delayed and ameliorated EAE symptoms by reducing EAE-related inflammation in the mouse CNS and reducing encephalitogenic Th1 and Th17 cells in the peripheral lymphoid organs. We observed that dimer intervention at a concentration of 1.2 nM suppressed MOG35-55 peptide-specific 2D2 transgenic T cells (2D2 T cells) proliferation by over 90% after in vitro activation with MOG35-55 peptide. The mechanisms involved in this antigen-specific dimer-mediated suppression were found to be downregulated TCR-CD3 expression as well as upregulated expression of membrane-bound TGF-β (mTGF-β) and IL-10 suppressive cytokines by the autoreactive CD4(+) T cells. Collectively, our data demonstrates that soluble divalent MHC class II molecules can abrogate pathogenic T cells in EAE. Furthermore, our data suggests that this strategy may provide an efficient and clinically useful option to treat autoimmune diseases. |
format | Online Article Text |
id | pubmed-3471819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34718192012-10-17 Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells Gong, Yeli Wang, Zhigang Liang, Zhihui Duan, Hongxia Ouyang, Lichen Yu, Qian Xu, Zhe Shen, Guanxin Weng, Xiufang Wu, Xiongwen PLoS One Research Article The MOG35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice is a useful animal model to explore therapeutic approaches to T cell-mediated autoimmune diseases because the dominant T-cell epitope(s) have been defined. It is rational that antigen-specific immunosuppression can be induced by using MHC-peptide complexes as specific TCR ligand(s) that interact with autoreactive T cells in the absence of co-stimulation. In this study, a soluble divalent MOG35-55/I-A(b) fusion protein (MOG35-55/I-A(b) dimer) was constructed to specifically target the autoreactive CD4(+) T cells in the EAE mouse. Intraperitoneal administration of the MOG35-55/I-A(b) dimer significantly delayed and ameliorated EAE symptoms by reducing EAE-related inflammation in the mouse CNS and reducing encephalitogenic Th1 and Th17 cells in the peripheral lymphoid organs. We observed that dimer intervention at a concentration of 1.2 nM suppressed MOG35-55 peptide-specific 2D2 transgenic T cells (2D2 T cells) proliferation by over 90% after in vitro activation with MOG35-55 peptide. The mechanisms involved in this antigen-specific dimer-mediated suppression were found to be downregulated TCR-CD3 expression as well as upregulated expression of membrane-bound TGF-β (mTGF-β) and IL-10 suppressive cytokines by the autoreactive CD4(+) T cells. Collectively, our data demonstrates that soluble divalent MHC class II molecules can abrogate pathogenic T cells in EAE. Furthermore, our data suggests that this strategy may provide an efficient and clinically useful option to treat autoimmune diseases. Public Library of Science 2012-10-15 /pmc/articles/PMC3471819/ /pubmed/23077616 http://dx.doi.org/10.1371/journal.pone.0047435 Text en © 2012 Gong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gong, Yeli Wang, Zhigang Liang, Zhihui Duan, Hongxia Ouyang, Lichen Yu, Qian Xu, Zhe Shen, Guanxin Weng, Xiufang Wu, Xiongwen Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells |
title | Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells |
title_full | Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells |
title_fullStr | Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells |
title_full_unstemmed | Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells |
title_short | Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells |
title_sort | soluble mog35-55/i-a(b) dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic t cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471819/ https://www.ncbi.nlm.nih.gov/pubmed/23077616 http://dx.doi.org/10.1371/journal.pone.0047435 |
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